PROJECT SUMMARY/ABSTRACT Age-related macular degeneration and ischemic retinal diseases, which include proliferative diabetic retinopathy, ischemic retinal vein occlusion and retinopathy of prematurity, are major causes of vision loss. The use of anti-VEGF agents has transformed the treatment of such disorders. However, not all patients respond to anti-VEGF therapy and there is currently considerable interest in not only augmenting the efficacy of VEGF inhibitors but also in treating non-responders. We propose to undertake a systematic investigation of the novel natural products produced by marine bacteria for their selective ability to inhibit basal or VEGF- stimulated proliferation of cultured endothelial cells, without affecting viability of normal retinal pigment epithelial cells. Molecules that fulfill these criteria will be tested in animal models of ischemic retinal disease and choroidal neovascularization. Our studies might provide an alternative, potentially longer lasting and more effective, than anti-VEGF therapy.